Gene pair based prognostic signature for colorectal colon cancer.
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ABSTRACT:
SUBMITTER: Shu P
PROVIDER: S-EPMC6211904 | biostudies-literature | 2018 Oct
REPOSITORIES: biostudies-literature
Publications
Gene pair based prognostic signature for colorectal colon cancer.
Shu Peng P Wu Jianping J Tong Yao Y Xu Chunxia C Zhang Xingguo X
Medicine 20181001 42
<h4>Background</h4>The identification of high-risk colorectal cancer (CRC) patient is key to individualized treatment after surgery and reliable prognostic biomarkers are needed identifying high-risk CRC patients.<h4>Methods</h4>We developed a gene pair based prognostic signature that could can the prognosis risk in patients with CRC. This study retrospectively analyzed 4 public CRC datasets, and 1123 patients with CRC were divided into a training cohort (n = 300) and 3 independent validation co ...[more]
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Project description:BackgroundHypermutated colorectal cancer (CRC) reportedly accounts for 15%-17% of all cases of CRC. However, the proportion and number of patients with hypermutated CRC cannot be unappreciated. Additionally, therapy options for these patients differ from those for CRC patients, with a greater potential benefit from immunotherapy.Materials and methodsWe sequenced the tumor mucosa of CRC patients with >24 months of follow-up data at our center and identified mutation profiles of hypermutated CRC as a training data set (Zhejiang University [ZJU]); we then collected patients from The Cancer Genome Atlas (TCGA) as a validation data set. Recurrently mutated genes were combined to calculate a compound score via Cox proportional hazards model. Patients with higher-than-median scores were segregated as the high-risk group. Outcomes were analyzed by Kaplan-Meier and Cox regression analyses using Python (3.6.0) and R (3.4.0).ResultsWe constructed a 4-gene signature (ACVR2A, APC, DOCK2, and POLE), with training in 45 hypermutated patients at ZJU and validation in 24 hypermutated patients from TCGA. Patients in the high-risk group showed poor survival (adjusted HR =9.85, 95% CI: 2.07-46.81, P=0.004). Further subgroup analysis was performed for stage II and III colon cancer (HR =10.91, 95% CI: 1.36-87.5, P=0.005) and high microsatellite instability (MSI-H) CRC (HR =12.57, 95% CI: 1.57-100.69, P=0.002) subgroups, which verified that our signature is universal. We then compared our prognostic signature with other risk factors (including MSI status, POLE driver mutation, BRAF-p.V600E, tumor mutational burden, and TNM staging). The results proved that our 4-gene signature is better than the other risk factor for prognosis in hypermutated CRC.ConclusionOur 4-gene signature is a good predictor of survival for hypermutated CRC, and this signature is powerful in stage II and III colon cancer and MSI-H CRC. Future prospective studies are needed to confirm the power of the 4-gene signature in patients receiving immunotherapy.
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